Oral squamous cell carcinoma (OSCC), the predominant malignancy of the oral cavity, is characterized by high rates of local recurrence, metastasis, and therapeutic resistance, contributing to persistently poor survival outcomes. The cancer stem cell (CSC) paradigm offers a compelling biological explanation for these clinical challenges. This paper provides a comprehensive examination of CSCs in oral neoplasms, elucidating their identification, molecular regulation, and pivotal role in tumor initiation, progression, and treatment failure. We detail the characteristic biomarkers used to isolate oral CSCs including CD44, ALDH1, CD133, and epithelial-specific antigen (ESA) and the core signaling pathways (Notch, Hedgehog, Wnt/β-catenin, and Bmi-1) that govern their self-renewal and survival. A critical analysis reveals that CSCs exhibit intrinsic resistance to conventional chemotherapy and radiotherapy through enhanced DNA repair capacity, upregulation of drug efflux pumps, activation of anti-apoptotic pathways, and a quiescent cell-cycle state. These properties enable CSCs to survive initial treatment and subsequently drive tumor recurrence and metastatic dissemination. The clinical implications are profound: a tumor's CSC burden may correlate with advanced stage, nodal metastasis, and worse prognosis. Moving beyond conventional cytotoxic approaches, this paper explores emerging therapeutic strategies specifically targeting the CSC compartment. These include pathway-specific inhibitors, agents targeting the CSC niche, differentiation therapy, and immunotherapeutic approaches leveraging CSC-specific antigens. We conclude that successfully eradicating oral CSCs, or disrupting their maintenance circuits, represents the most promising avenue for achieving durable cures and preventing recurrence in OSCC. Integrating CSC-targeted agents with standard therapies in a rational, biomarker-driven manner may fundamentally transform the therapeutic landscape for this devastating disease.